The candidate, Jama L. Purser, PT, MS, PhD, is an Epidemiologist with degrees in Physical Therapy and Movement Science. Her doctoral and post-doctoral training focused on trajectories of disability in aging populations. She now proposes to add a genetic component to her training, including coursework and mentorship in genetics, proteomics, and Bayesian statistics. Her long-term goal is to become an independent investigator in a new area of disablement research, focusing on observational studies of the genetic epidemiology of sarcopenia, physical performance and disability as well as clinical studies of genomic and proteomic medicine. Recent work suggests that genotypic variation may contribute to phenotypic patterns of sarcopenia, physical performance and disability among older adults, and that such genetic influence may operate through biological pathways independent of, or complementary to, the effects of disease and comorbidity. These pathways are not yet fully understood. While recent work has focused on static, disease-based phenotypes identified at a single time point, few studies have evaluated candidate gene effects on dynamic trajectories of sarcopenia, physical performance and disability over time. The specific aim is to investigate longitudinal disability-related phenotypes and their association with hypothesized genetic mechanisms (e.g. insulin-signaling, calcium channel function, and osmotic regulation). Candidate genes from several biological pathways will be studied, focusing on those potentially related to sarcopenia and physical frailty of aging. Two cohorts will be used: 1) the Duke Established Populations for Epidemiologic Studies of the Elderly (n=1757), a geographically representative sample (age 65-105, followed for 10 years), and 2) the Health, Aging and Body Composition Study (n=3,075), a random sample of community residents (age 70-79, followed for 6 years). The Duke EPESE cohort includes physical performance and disability phenotypes; the Health ABC dataset includes longitudinal muscle mass, sarcopenia and physical performance. Evaluated findings will improve public health understanding of the etiology of physical frailty. Results should also indicate directions for further disability-related genetic studies and interventions. [unreadable] [unreadable] [unreadable] [unreadable]